Cell Biology Lecture 38: Cancer Genetics + Oncogenes

(Benign vs Malignant Tumors) Do benign tumors penetrate adjacent tissue borders?

No

(Benign vs Malignant Tumors) Do benign tumors grow slowly or quickly?

Slowly

(Benign vs Malignant Tumors) Do benign tumors metastasize (spread)?

No

(Benign vs Malignant Tumors) Are benign tumors well differentiated?

Yes

(Benign vs Malignant Tumors) What do benign tumors closely resemble?

Tissue of origin in morphology and function

(Benign vs Malignant Tumors) Do malignant tumors penetrate adjacent tissue borders?

Yes

(Benign vs Malignant Tumors) Do malignant tumors grow slowly or quickly?

Quickly

(Benign vs Malignant Tumors) What are common in malignant tumors?

Necrosis and hemorrhage

(Benign vs Malignant Tumors) Do malignant tumors metastasize (spread)?

Yes

(Benign vs Malignant Tumors) Do more aggressive malignancies have cells with more or less fidelity to their precursors?

Less

(Benign vs Malignant Tumors) What are malignant neoplasms with undifferentiated cells called?

Anaplastic

(Benign vs Malignant Tumors) Is hepatoma benign or malignant?

Malignant

(Benign Tumors) What is a benign tumor of the epithelium that exhibits a branched, exophytic growth pattern?

Papilloma

(Benign Tumors) What is a growth that projects above a mucosal surface; usually restricted to benign neoplasms?

Polyp-

(Benign Tumors) What is a proliferation that demonstrates glandular differentiation?

Adenoma

(Benign Tumors) What is a tumor that arises from germ cells and contains derivatives of all of the germ layers? (Usually found in gonads)

Teratoma

(Benign Tumors) What is a localized overproliferation of disorganized but mature (differentiated) cells indigenous to that particular area?

Hamartoma

(Benign Tumors) What is a well organized (normal) tissue in an abnormal location?

Choristoma

(Malignant Tumors) What occurs with malignant tumors?

1. Increased cellularity

2. Increased cell size

3. Increased nuclear to cytoplasmic ratio

4. Pleomorphisms

5. Abnormal mitosis

6. Loss of cohesion

7. Necrosis

(Malignant Tumors) What is a malignant tumor of epithelial origin?

Carcinoma

(Malignant Tumors) What is a carcinoma of gastric mucosa?

Gastric Adenocarcinoma

(Malignant Tumors) What is a carcinoma of skin or mucosa?

Squamous Cell Carcinoma

(Malignant Tumors) What is a carcinoma of the bladder epithelium?

Transitional Cell Carcinoma

(Malignant Tumors) What is a malignant tumor of mesenchymal origin?

Sarcoma

(Malignant Tumors) What is a sarcoma of cartilaginous origin?

Chondrosarcoma

(Malignant Tumors) What is a sarcoma that demonstrates osseous differentiation?

Osteosarcoma

(Malignant Tumors) What is a sarcoma of fibrous connective tissue?

Fibrosarcoma

(Malignant Tumors) What is a malignant tumor of melanocytes?

Melanoma

(Malignant Tumors) What is a malignant tumor of the testes?

Seminoma

(Malignant Tumors) What is a malignant tumor of the lymphocytes?

Lymphoma

(Malignant Tumors) What is a malignant tumor of hematopoietic cells?

Leukemia

(Malignant Tumors) What is a malignant tumor of plasma cells?

Myeloma

(Malignant Tumors) What do carcinomas use to metastasize?

Lymphatics

(Malignant Tumors) What do sarcomas use to metastasize?

Blood

(Genetics of Cancer) What are the genes that must be balanced for cell growth/proliferation?

1. Oncogenes

2. Tumor Suppressors

(Genetics of Cancer) What is Knudson's two hit hypothesis?

Tumor suppressor genes need both alleles to be activated in order for phenotypic change

(Genetics of Cancer) Which tumor suppressor gene is related to Knudson's two hit hypothesis?

Rb

(Tumor Suppression) What is the most frequently observed somatic gene event in human cancer?

Alteration of p53 gene (tumor suppressor)

(Tumor Suppression) What syndrome are p53 alterations found in?

Li-Fraumeni Syndrome

(Tumor Suppression) What is Li-Fraumeni Syndrome characterized by?

1. Early onset breast cancer

2. Sarcomas

(Tumor Suppression) What syndrome is the result of a mutation in PTEN?

Cowden Syndrome

(Tumor Suppression) What syndrome is the result of a mutation in p57?

Beckwith-Wiedemann Syndrome

(Tumor Suppression) What syndrome is the result of Rb loss?

Retinoblastoma

(Alcohol + Tobacco Cancers) What is the receptor that is overactivated by alcohol and tobacco cancers and activates other pathways for malignant growth?

Epidermal Growth Factor Receptor (EGFR)

(Alcohol + Tobacco Cancers) What are the pathways that are activated by EGFR and contribute to malignant growth?

1. Ras (MAPK)

2. PI3K/AKT

(Alcohol + Tobacco Cancers) What does the dysregulation of NF-kB promote?

1. Tumor angiogenesis

2. Metastasis

3. Treatment resistance

(Alcohol + Tobacco Cancers) What is the most common mutated gene in alcohol and tobacco cancers?

p53

(Alcohol + Tobacco Cancers) Which is the tumor suppressant gene that is inactivated in alcohol and tobacco cancers?

p16

(Alcohol + Tobacco Cancers) Which cancer is the most commonly associated with alcohol and tobacco cancer?

Squamous cell carcinoma of head and neck

(Alcohol + Tobacco Cancers) How much more risk of oral cancer is there for smokers and drinkers?

15 times greater

(Cell Cycle) In what phase does replication of DNA occur?

S-phase

(Cell Cycle) In what phase does mitosis occur?

M-phase

(Cell Cycle) Which phases are in interphase?

G1, S, G2

(Cell Cycle) What are the three types of cells in G0-phase?

1. Permanent

2. Labile

3. Stable

(Cell Cycle) Which cells can re-enter the cell cycle from G0-phase?

Stable cells

(Cell Cycle) What are the three regulators of the cell cycle?

1. Cyclins

2. Cyclin-dependent Kinases (CDKs)

3. Cyclin-dependent Kinase Inhibitors (CKIs)

(Cell Cycle) Which cyclin promotes DNA replication in S and progresses into G2?

Cyclin A

(Cell Cycle) Which cyclin peaks near the end of G2 and is degraded during M?

Cyclin B

(Cell Cycle) If cyclins A and B are not degraded through ubiquitin-dependent proteolysis, what happens?

Cell is arrested in M-phase

(Cell Cycle) Which cyclins reach maximum levels in mid-to-late G1 and are required to pass the restriction point (R)?

Cyclin D1, D2, D3, E

(Cell Cycle) What needs to pair with each other in vivo to phosphorylate Rb?

Cyclin D1 and CDK4/6

(Cell Cycle) Why must Rb be phosphorylated?

To drive cell cycle

(Cell Cycle) Is Rb a tumor suppressor gene?

Yes

(Cell Cycle) Which cyclin accumulates (spikes) in G1 and reaches its maximum level as the cell enters S?

Cyclin E

(Cell Cycle) What does cyclin E binds to for progression into S?

CDK2

(Cell Cycle) What happens during G1 phase?

Synthesis of cyclin D is increased

(Cell Cycle) What is promoted when cyclin D partners with CDK4/6 in G1?

1. Cell cycle entry

2. Progression through G1 to S

(Cell Cycle) What is controlled by the CDK2 and cyclin A interaction in S?

Phosphorylation of targets involved in DNA replication

(Cell Cycle) What is the primary regulator of the cell cycle in G2?

CDK1

(Cell Cycle) What do CKIs ensure?

That DNA damage during cell cycle was repaired

(Cell Cycle) How do CKIs ensure repairment?

1. Arrest growth and initiate repair

2. Apoptosis

(Cell Cycle) What CKI is the downstream of p53?

p21

(Cell Cycle) Which CKI blocks cyclin bound CDK4/6 to inhibit growth?

p16

(Cell Cycle) Which loss of CKI leads to development of endocrine tumors?

p27

(Cell Cycle) What does Rb bind to in order to drive the cell cyle?

E2F

(Cell Cycle) What signaling pathway leads to hypophosphorylation of Rb and cell cycle arrest?

p53-p21-Rb signaling

(Cell Cycle) Is hypophosphorylated Rb an active tumor suppressor?

Yes

(Cell Cycle) What happens to hyperphosphorylated Rb?

Loses tumor suppression ability

(Cell Cycle) Which CKI inhibits G1 phase cyclin-CDK complexes?

p21

(HPV Cancer) What are the high risk HPV types?

16, 18, 31, 32

(HPV Cancer) What is high risk HPV types associated with?

Oropharyngeal squamous cell carcinomas

(HPV Cancer) Are HPV cancers less or more differentiated than tobacco cancers?

Less

(HPV Cancer) Do HPV cancers have worse or better prognosis than tobacco cancers?

Better Prognosis

(HPV Cancer) Do HPV cancers exhibit loss of p53 or p16?

No

(HPV Cancer) What is elevated in HPV cancers?

p16

(HPV Cancer) Is p53 mutated in HPV cancers?

No, but it is inhibited

(HPV Cancer) Which protein aids in the process of viral DNA replication?

E2

(HPV Cancer) Which protein promotes the degradation of p53?

E6

(HPV Cancer) Which protein binds and inactivates Rb?

E7

(HPV Cancer) Which protein regulates E6 and E7?

E2

(HPV Cancer) What happens if E7 inhibits pRb?

S-phase progression

(HPV Cancer) Which HPV is low risk and cause papillomas?

Squamous papilloma

(HPV Cancer) Which HPV is high risk and cause cervical cancer?

Cervical dysplasia

(UV Radiation Cancer) What is the result of clonal expansion of UVB-transformed keratinocytes?

Actinic Cheilitis

(UV Radiation Cancer) What is actinic cheilitis characterized by?

Genomic instabiliy

(UV Radiation Cancer) What does UVB induce?

Formation of aberrant covalent bonds between adjacent pyrimidine bases

(UV Radiation Cancer) What can UVB cause mutations in during the initiation stage of actinic-induced carcinogenesis?

p53

(UV Radiation Cancer) How is actinic cheilitis expressed on the lips?

Loss of vermillion border

(UV Radiation Cancer) Does actinic cheilitis cause dysplasia?

Yes

(Squamous Cell Carcinoma) What are the three classifications for squamous cell carcinoma?

1. Skin

2. Oral Cavity

3. Pharynx